Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
Authors: Jerry Guintivano, Enda M. Byrne, Jacqueline Kiewa, Shuyang Yao, Anna E. Bauer, Karolina A. Aberg, Mark J. Adams, Archie Campbell, Megan L. Campbell, Karmel W. Choi, Elizabeth C. Corfield, Alexandra Havdahl, Donald Hucks, Nastassja Koen, Yi Lu, Merete L. Mægbæk, Jimmy Mullaert, Roseann E. Peterson, Laura M. Raffield, Hannah M. Sallis, Julia M. Sealock, Alicia Walker, Hunna J. Watson, Ying Xiong, Jessica M.K. Yang, Richard J.L. Anney, Katherine Gordon-Smith, Leon Hubbard, Lisa A. Jones, Raluca Mihaescu, Mette Nyegaard, Antonio F. Pardiñas, Amy Perry, Nazmus Saquib, Aladdin H. Shadyab, Alexander Viktorin, Ole A. Andreassen, Tim B. Bigdeli, Lea K. Davis, Cindy-Lee Dennis, Arianna Di Florio, Caroline Dubertret, Yen-Chen A. Feng, Benicio N. Frey, Sophie Grigoriadis, Emilie Gloaguen, Ian Jones, James L. Kennedy, Holly Krohn, Theodora Kunovac Kallak, Yun Li, Nicholas G. Martin, Andrew M. McIntosh, Jeannette Milgrom, Trine Munk-Olsen, Tim Oberlander, Catherine M. Olsen, Nicolas Ramoz, Ted Reichborn-Kjennerud, Emma Robertson Blackmore, David Rubinow, Alkistis Skalkidou, Jordan W. Smoller, Dan J. Stein, Zachary N. Stowe, Valerie Taylor, Sarah Tebeka, Martin Tesli, Ryan J. Van Lieshout, Edwin J.C.G. van den Oord, Simone N. Vigod, Thomas Werge, Lars T. Westlye, David C. Whiteman, Heather J. Zar, Naomi Wray, Samantha Meltzer-Brody, Patrick Sullivan
Journal: American Journal of Psychiatry (2023)

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability , 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).